Quantitative histochemical studies of microscopic samples of the cochlea and the cochlear nucleus will be done. Enzyme activities, metabolite levels and rates of end-product formation by major pathways can be used as indicators of biochemical mechanisms. The research will progress in three phases, each of which will proceed following this same rationale: 1.) The peculiarities of energy metabolism, of transcellular transport systems, of transmitter metabolism and, if feasible, of cyclic nucleotide and prostaglandin metabolism, of protein and RNA synthesis will be investigated by comprehensive characterization through direct biochemical analysis of a) the enzyme patterns (e.g. of the GABA shunt), of b) the intermediate levels (e.g. of glycolysis) and of c) the activity of product formation of the major pathways (e.g. GABA). 2.) Simple experimental conditions will be used to decrease or increase the rate of flux through the major pathways by using established pathophysiological (e.g. ischemia, hypoglycemia, hyperglycemia) and pharmacological measures (e.g. iodoacetate, salicylate, ouabain) and to study the effect of such alterations on the three defined parameters. 3.) Based on the knowledge accumulated in the previous stages, experiments will be designed which will assess the influence of deafferentation, of physiological tone stimulation, of noise trauma and of ototoxic drugs on these defined parameters. BIBLIOGRAPHIC REFERENCES: Levels of Putative Transmitter Amino Acids in Guinea Pig Cochlea, D. A. Godfrey, J. A. Carter, S. J. Berger, F. M. Matschinsky, J. Histochem. Cytochem. 24, 468-470 (1976). Activities of Enzymes of the Cholinergic System in the Guinea Pig Cochlea, D. A. Godfrey, J. J. Urzanowski, Jr., F. M. Matschinsky, J. Histochem. Cytochem. 24, 470-472 (1976).